UCSF neuroscientists are chasing some particularly hairy leads into the molecular pathways of pain.

Researchers, led by David Julius, a professor and chairman of the UCSF physiology department, and postdoctoral researcher Jan Siemens, report today that the venomous bite of a common West Indies tarantula hurts for the same reason chile peppers burn your tongue.

The finding appears to be the first documented example of a plant and an animal targeting a particular type of heat and pain sensor -- known as the capsaicin receptor -- found in the skin of their predators. Both the plants and the tarantulas target the receptor to defend against their enemies -- unwary monkeys, perhaps, in the case of the arboreal tarantulas, or hungry insects in the case of the pepper plants.

Scientists already knew what made the chiles hot. In the new experiments, detailed in the latest issue of the journal Nature, they used laboratory mice, which have the same pain sensors as humans, to see if spider venom might work the same way. Results could help unravel the molecular basis of pain and lead to new kinds of analgesics or anti-inflammatory drugs.

The UCSF researchers focused on P. cambridgei, commonly known as the Trinidad chevron for its distinctive abdominal markings, a fuzzy but not exactly cuddly tree dweller of the tropics.

The tarantula, which can grow to be about 6 inches long as an adult, is an aggressive, skittish predator that sports fangs as big as a rattlesnake's and has an appetite for anything that moves, up to the size of a baby mouse.

It's also a crawling chemistry set.

Its bite delivers, among other things, three novel peptides -- bits of protein material -- that activate the capsaicin receptor. When that happens, a gate for electrically charged particles opens allowing the ions to flow into a nerve cell. Local inflammation occurs at the wound, and signals are sent to the brain that are typically interpreted as burning pain -- providing a compelling reason to avoid the Trinidad tarantula.

The active ingredient in chile peppers does precisely the same thing, even if chefs have learned to keep dosages within a more palatable range. Some mustard and menthol plants target this same receptor family, which includes about 30 types.

Drug developers are keen to get a detailed understanding of the molecules that underlie pain sensations.

"A lot of pharmaceutical companies are looking at these ion channels, and toxins have been incredibly valuable studying structure and activity," Julius said.

Julius and his colleagues have studied the venom of 22 spiders and scorpions, all known for painful stings and bites, in a search for specific components that would activate the capsaicin pain receptors.

One other spider also showed capsaicin-like activity, but the researchers focused mainly on the Trinidad tarantula.

They obtained the venom from an Arizona company called Spider Pharm, whose founder and president, Charles Kristensen, took up spiders as a hobby 25 years ago. Now, he spends much of his time milking black widows for commercial anti-venom testing.

The newly discovered venom ingredients clearly aren't for the squeamish, suggested even by their formal name: "ICK peptides." The acronym stands for "inhibitory cysteine knot." Kristensen, a dedicated arachnophile who has recently started developing educational programs for schoolchildren, insisted it's not as nasty a business as it sounds.

Spiders generally resort to the pain weapon only to scare away bigger animals, and most aren't terribly poisonous. They prefer to incapacitate their prey, Kristensen said, so the insect can be partly digested and eaten without running off. Sometimes, the bite comes with a kind of sedative, seasoned perhaps with some regurgitated digestive enzymes, that allows the prey to stay alive just long enough for the enzymes to circulate.

Then the spider can drink its liquefied soup of predigested, blissed-out insect with minimal fuss. Just don't interrupt dinner.

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